Biomarkers may be used to monitor and treat progression of a disease or disorder. A biomarker has traditionally been a biochemical molecule whose presence and level is established as being closely and specifically related to a particular aspect of biological function or a disease process, and for which methods of reliable and quantifiable measurements have been developed. As applied to disease, biomarkers can be useful for the sensitivity they bring to a diagnostic process, where their presence can detect disease at an early stage, or when other clinical manifestations of the disease are not fully manifested, such that diagnosis can be difficult. Inasmuch as biomarkers can be used to monitor a disease once it has been diagnosed, they can be used to measure the effectiveness of treatments for the disease. Often, it takes time for treatment to allow easily observable clinical improvement, and thus, as with diagnosis, a biomarker can provide an indication of treatment effectiveness before clinical improvement is obvious. Additionally, clinical indications of improvement can be difficult to quantify, and can be masked by clinical factors not directly tied to the disease. Thus, biomarkers are useful in detecting in effectiveness of treatment, as in determining, for example, the effectiveness of a drug, or any form of physical or electrical intervention.
Amyotrophic lateral sclerosis is difficult to diagnose at an early stage, and it is difficult to discern the rate of progression of disease, especially once therapy has been initiated. For some time, there has been a concerted effort to identify benchmarks or biomarkers useful in detecting the presence of ALS and the rate of its progression. To provide the basic features of biomarkers, such as being closely and specifically associated with the disease, and being quantifiable, a biomarker need not necessarily be a particular molecule. An effective biomarker may, for example, simply be a physiological measurement of a parameter that closely and specifically varies or manifests as a function of the presence or severity of the disease.
A number of physiologically measured or qualitatively assessed parameters have been investigated as biomarkers (benchmarks) for their ability to predict survival in ALS patients or as a surrogate predictor of disease progression. There are currently no biomarkers exclusively associated with ALS, or directly tied to the aspects of the disease process that underlie the clinical status of the patient and especially markers having sufficient sensitivity or resolution with regard to changes in the level of the disease. There is a need, therefore, for effective biomarkers for ALS, particularly those that are closely and specifically associated with the disease, that are quantifiable, that are cost-effective, that can be processed quickly into useful data, and that can be easily worked into the ongoing context of patient care.
The methods, devices and systems described herein have been developed from the surprising observation that the electromyographic measurements made from the same location of the same patient's diaphragm over time can provide a remarkably sensitive measure of the presence or progression of ALS, and the efficacy of treatment of ALS. Although the initial observations were made in ALS patients, the methods, devices and systems described may be applied to other neurological (neurodegenerative) diseases and disorders.